Mimicry of the proton wire mechanism of enzymes inside a supramolecular capsule enables ß-selective O-glycosylations.

Enzymes achieve high substrate and product selectivities by orientating and activating the substrate(s) appropriately inside a confined and finely optimized binding pocket. Although some basic aspects of enzymes have already been mimicked successfully with man-made catalysts, substrate activation by proton wires inside enzyme pockets has not been recreated with man-made catalysts so far. A proton wire facilitates the dual activation of a nucleophile and an electrophile via a reciprocal proton transfer, enabling highly stereoselective reactions under mild conditions. Here we present evidence for such an activation mode inside the supramolecular resorcin[4]arene capsule and demonstrate that it enables catalytic and highly ß-selective glycosylation reactions-still a major challenge in glycosylation chemistry. Extensive control experiments provide very strong evidence that the reactions take place inside the molecular container. We show that this activation strategy is compatible with a broad scope of glycoside donors and nucleophiles, and is only limited by the cavity size.

Expanding the Protecting Group Scope for the Carbonyl Olefin Metathesis Approach to 2,5-Dihydropyrroles.

Chiral pyrrolidine derivatives are important building blocks for natural product synthesis. Carbonyl olefin metathesis has recently emerged as a powerful tool for the construction of such building blocks from chiral amino acid derivatives. Here, we demonstrate that the supramolecular resorcinarene catalyst enables access to chiral 2,5-dihydropyrroles under Brønsted acid catalysis. Moreover, this catalytic system even tolerated Lewis-basic-protecting groups like mesylates that are not compatible with alternative catalysts. As expected for conversion inside a closed cavity, the product yield and selectivity depended on the size of the substrates.